Improved Syntheses of the Naturally Occurring Glycosidase Inhibitor Salacinol

Abstract

Improved syntheses of the naturally occurring sulfonium ion, salacinol are described. Salacinol is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of Type 2 Diabetes. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl- or 2,3,5-tri-O-p-methoxybenzyl- 1 ,4-anhydro-4-thio-D-arabinitol at the least hindered carbon of benzylidene-protected L-erythritol-1,3-cyclic sulfate in 1,1,1,3,3,3-hexafluoro-2-propanol as solvent. The reactions are compared to those with the benzyl-protected L-erythritol-1.3-cyclic sulfate and also to those in acetone and 2-propanol. Excellent yields are obtained for the reactions with the benzylidene-protected cyclic sulfate. The synthetic route employing p-methoxybenzyl ether protecting groups is advantageous since all protecting groups in the adduct may be removed with trifluoroacetic acid to yield salacinol, thereby obviating the problematic deprotection of benzyl ethers by hydrogenolysis.